This translational research proposal addresses the epidemiology, biology and treatment of children with the related preleukemic conditions juvenile chronic myelogenous leukemia and bone marrow monosomy 7 syndrome (JCML/Mo7). These disorders share a number of major clinical features that suggest they are related pathogenically; however, the precise relationship between them is uncertain. Treatment results in children with JCML/Mo7 have been dismal even with allogeneic bone marrow transplantation. This proposal is based upon recent epidemiological findings linking specific obstetric and parental occupational risk factors with the development of myeloid leukemia during infancy; upon the observation that some children with JCML have show clinical responses to the differentiating agent cis retinoic acid; and upon molecular genetic and biochemical studies that implicate deregulated signaling through the p21 ras family of proteins in the pathogenesis of these malignant myeloid disorders. We will test the hypothesis that JCML/Mo7 are associated with genetic and acquired risk factors which correlate with specific molecular and cytogenetic alterations in patient bone marrows, and that these molecular markers will be of prognostic value and can be used to measure responses to treatment.